tbuckley/cabot-search huggingface dataset:
Risk factors for severe infection and mortality In patients with <scp>COVID</scp>‐19 in patients with multiple myeloma and <scp>AL</scp> amyloidosis
Authors: Matthew Ho, Saurabh Zanwar, Francis K. Buadi, Sikander Ailawadhi, Jeremy Larsen, Leif Bergsagel, Moritz Binder, Asher Chanan‐Khan, David Dingli, Angela Dispenzieri, Rafael Fonseca, Morie A. Gertz, Wilson Gonsalves, Ronald S. Go, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Eli Muchtar, Vivek Roy, Taimur Sher, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi L. Hwa, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: American Journal of Hematology (2022)

Patients with multiple myeloma (MM) have a lower efficacy from COVID-19 vaccination and a high rate of mortality from COVID-19 in hospitalized patients. However, the overall rate and severity of COVID-19 infection in all settings (including non-hospitalized patients) and the independent impact of plasma cell-directed therapies on outcomes needs further study. We reviewed the medical records of 9225 patients with MM or AL amyloidosis (AL) seen at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 and identified 187 patients with a COVID-19 infection (n = 174 MM, n = 13 AL). The infection rate in our cohort was relatively low at 2% but one-fourth of the COVID-19 infections were severe. Nineteen (10%) patients required intensive care unit (ICU) admission and 5 (3%) patients required mechanical ventilation. The mortality rate among hospitalized patients with COVID-19 was 22% (16/72 patients). Among patients that were fully vaccinated at the time of infection (n = 12), two (17%) developed severe COVID-19 infection, without any COVID-related death. On multivariable analysis, treatment with CD38 antibody within 6 months of COVID-19 infection [Risk ratio (RR) 3.6 (95% CI: 1.2, 10.5), p = .02], cardiac [RR 4.1 (95% CI: 1.3, 12.4), p = .014] or pulmonary comorbidities [RR 3.6 (95% CI 1.1, 11.6); p = .029] were independent predictors for ICU admission. Cardiac comorbidity [RR 2.6 (95% CI: 1.1, 6.5), p = .038] was an independent predictor of mortality whereas MM/AL in remission was associated with lower mortality [RR 0.4 (95% CI: 0.2-0.8); p = .008].
Cutaneous T‐cell lymphomas: 2023 update on diagnosis, risk‐stratification, and management
Authors: Alexandra C. Hristov, Trilokraj Tejasvi, Ryan A. Wilcox
Journal: American Journal of Hematology (2022)

Abstract Disease Overview Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell neoplasms involving the skin, the majority of which may be classified as Mycosis Fungoides (MF) or Sézary Syndrome (SS). Diagnosis The diagnosis of MF or SS requires the integration of clinical and histopathologic data. Risk‐Adapted Therapy TNMB (tumor, node, metastasis, blood) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral or the blood involvement are generally approached with systemic therapies, including biologic‐response modifiers, histone deacetylase inhibitors, or antibody‐based strategies, in an escalating fashion. In highly‐selected patients, allogeneic stem‐cell transplantation may be considered, as this may be curative in some patients.
Abstract 13038: A New Four-parameter Echocardiographic Score to Predict Mortality in Inoperable Aortic Stenosis Patients
Authors: Wendy Tsang, Ivan S Salgo, Mark Gajjar, M. Cristina Abduch, Benjamin H Freed, Lynn Weinert, Roberto M Lang
Journal: Circulation (2013)

Background: The Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score is used to risk stratify patients for transcatheter aortic valve replacement (TAVR). However, calculation of the STS score requires compilation of 24 parameters. We examined the prognostic value of: 1) STS score alone; 2) STS score with various transthoracic echocardiographic (TTE) parameters; and 3) TTE parameters without STS score in predicting mortality in patients with severe aortic stenosis (AS) ineligible for surgical valve replacement. Methods: Baseline demographics, TTE parameters, STS scores and clinical outcomes at an average follow-up of 1.8 years were obtained from 106 (40 male, 79+10 yrs) medically-managed inoperable patients with severe AS undergoing TTE from January 2007 to February 2012. TTE predictors of mortality were identified from univariate analyses. Hierarchical, multivariable Cox regression models were constructed. C-index was used to compare non-nested models. Results: Overall mortality rate was 5...
Airway epithelial ITGB4 deficiency induces airway remodeling in a mouse model
Authors: Lin Yuan, Huijun Liu, Xizi Du, Ye Yao, Ling Qin, Zhenkun Xia, Kai Zhou, Xinyu Wu, Yunchang Yuan, Bei Qing, Yang Xiang, Xiangping Qu, Xiaoqun Qin, Ming Yang, Chi Liu
Journal: Journal of Allergy and Clinical Immunology (2022)
An international medical education
Authors: Anna Christina Morawski
Journal: BMJ (2022)

<h3>Objective:</h3> To describe a patient with <i>T398A</i> mutation in mitochondrial <i>ND5</i> gene that presented improvement in motor skills after CoQ10 supplementation. <h3>Background:</h3> <i>ND5</i> mutations have been described in patients with different clinical conditions, such as LHON, MELAS, Leigh-like syndrome and overlapping mitochondriopathy syndromes. The correct identification of mithocondrial genes is mandatory since they may have a response to CoQ10 therapy. <h3>Design/Methods:</h3> A 6-year-old boy presented with delayed milestones since birth. Neurological examination disclosed cognitive impairment and severe ataxia. Brain MRI showed cerebellar atrophy. Whole exome sequence analysis depicted homoplasmic mutation T398A in mitochondrial gene <i>ND5</i>. <h3>Results:</h3> The patient had a marked improvement after CoQ10 supplementation with doses up to 55 mg/kg/day. After six months in therapy, a marked improvement in speech, dysmetria, walking speed and ataxia was observed. Estimated scale for the assessment and rating of ataxia (SARA) had an improvement from 28 (before CoQ10 supplementation) to 19 points (six months after CoQ10 supplementation). <h3>Conclusions:</h3> This report demonstrates that <i>ND5</i> gene mutations should be investigated in suspected mithocondrial disorders and treatment with CoQ10 should be promptly considered. <b>Disclosure:</b> Dr. Pedroso has nothing to disclose. Dr. Drumond Gama has nothing to disclose. Dr. Arita has nothing to disclose. Dr. Ravagnani has nothing to disclose. Dr. Barros has nothing to disclose. Dr. Sanches has nothing to disclose. Dr. Picosse has nothing to disclose. Dr. Lopes has nothing to disclose. Dr. Aguiar has nothing to disclose. Dr. Chiaratti has nothing to disclose. Dr. Habermann Macabelli has nothing to disclose. Dr. Masruha has nothing to disclose. Dr. Barsottini has nothing to disclose. Dr. Quinzii Hirano has nothing to disclose. Dr. Hirano has received (royalty or license fee or contractual rights) payments from MitoRainbow Therapeutics, Inc. Dr. Ferreiro Barros has nothing to disclose.
Threshold protective levels of serum IgG to Shigella lipopolysaccharide: re-analysis of Shigella vaccine trials data
Authors: Dani Cohen, Shai Ashkenazi, Rachel Schneerson, Nahid Farzam, Anya Bialik, Shiri Meron-Sudai, Valeria Asato, Sophy Goren, Tomer Ziv Baran, Khitam Muhsen, Peter B. Gilbert, Calman A. MacLennan
Journal: Clinical Microbiology and Infection (2022)

Establishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis.We performed new analyses of serologic and vaccine efficacy (VE) data from two randomized vaccine-controlled trials of the Shigella sonnei-Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate conducted in young adults and children aged 1-4 years in Israel. Adults received either S. sonnei-rEPA (n = 183) or control vaccines (n = 277). Children received the S. sonnei-rEPA conjugate (n = 1384) or S. flexneri 2a-rEPA conjugate (n = 1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti-S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti-S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and the reverse cumulative distribution of IgG levels.Among adults, four vaccinees and 23 controls developed S. sonnei shigellosis; the VE was 74% (95% CI, 28-100%). A threshold of ≥1:1600 IgG anti-S. sonnei LPS titre was associated with a reduced risk of S. sonnei shigellosis and a predicted VE of 73.6% (95% CI, 65-80%). The IgG anti-S. sonnei LPS correlated with serum bactericidal titres. In children, a population-based level of 4.5 ELISA Units (EU) corresponding to 1:1072 titre, predicted VE of 63%, versus 71% observed VE in children aged 3-4 years. The predicted VE in children aged 2-4 years was 49%, consistent with the 52% observed VE.Serum IgG anti-S. sonnei LPS threshold levels can predict the degree of VE and can be used for the evaluation of new vaccine candidates.
Increasing adherence to the Mediterranean diet and lifestyle is associated with reduced fecal calprotectin and intra-individual changes in microbial composition of healthy subjects
Authors: L. Godny, L. Reshef, T. Sharar Fischler, S. Elial-Fatal, T. Pfeffer-Gik, B. Raykhel, K. Rabinowitz, A. Levi-Barda, TT. Perets, R. Barkan, I. Goren, JE. Ollech, H. Yanai, U. Gophna, I. Dotan
Journal: Gut Microbes (2022)

The Mediterranean diet (MED) is associated with the modification of gut microbial composition. In this pilot study, we investigate the feasibility of a microbiota-targeted MED-based lifestyle intervention in healthy subjects. MED intervention integrating dietary counseling, a supporting mobile application, and daily physical activity measurement using step trackers was prospectively applied for 4 weeks. Blood and fecal samples were collected at baseline, after the 4-week intervention, and at 6 and 12 months. Blood counts, inflammatory markers, microbial and eukaryotic composition were analyzed. Dietary adherence was assessed using daily questionnaires. All 20 healthy participants (females 65%, median age 37), completed the 4-week intervention. Adherence to MED increased from 15.6 ± 4.1 (baseline) to 23.2 ± 3.6 points (4 weeks), p < .01, reflected by increased dietary fiber and decreased saturated fat intake (both p < .05). MED intervention modestly reduced fecal calprotectin, white blood cell, neutrophil, and lymphocyte counts, within the normal ranges (P < .05). Levels of butyrate producers including Faecalibacterium and Lachnospira were positively correlated with adherence to MED and the number of daily steps. Bacterial composition was associated with plant-based food intake, while fungal composition with animal-based food as well as olive oil and sweets. Increasing adherence to MED correlated with increased absolute abundances of multiple beneficial gut symbionts. Therefore, increasing adherence to MED is associated with reduction of fecal calprotectin and beneficial microbial alterations in healthy subjects. Microbiota targeted lifestyle interventions may be used to modify the intestinal ecosystem with potential implications for microbiome-mediated diseases.
Children have a right to clean air, and we must fight for it to become a reality
Authors: Camilla Kingdon
Journal: BMJ (2022)

Legally binding targets based on WHO guidelines would reduce the number of deaths from air pollution in the UK." 1 This was the clear conclusion from the coroner following the death of nine-year-old Ella Adoo-Kissi-Debrah in 2013 following an asthma attack.Ella was the first person in the UK to have air pollution listed as a cause of death. 2 As paediatricians we are committed to learning from this very tragic example-no other child in the UK should be allowed to suffer the way that Ella did.
Neomorphic DNA-binding enables tumor-specific therapeutic gene expression in fusion-addicted childhood sarcoma
Authors: Tilman L. B. Hölting, Florencia Cidre-Aranaz, Dana Matzek, Bastian Popper, Severin J. Jacobi, Cornelius M. Funk, Florian H. Geyer, Jing Li, Ignazio Piseddu, Bruno L. Cadilha, Stephan Ledderose, Jennifer Zwilling, Shunya Ohmura, David Anz, Annette Künkele, Frederick Klauschen, Thomas G. P. Grünewald, Maximilian M. L. Knott
Journal: Molecular Cancer (2022)

Chimeric fusion transcription factors are oncogenic hallmarks of several devastating cancer entities including pediatric sarcomas, such as Ewing sarcoma (EwS) and alveolar rhabdomyosarcoma (ARMS). Despite their exquisite specificity, these driver oncogenes have been considered largely undruggable due to their lack of enzymatic activity.Here, we show in the EwS model that - capitalizing on neomorphic DNA-binding preferences - the addiction to the respective fusion transcription factor EWSR1-FLI1 can be leveraged to express therapeutic genes.We genetically engineered a de novo enhancer-based, synthetic and highly potent expression cassette that can elicit EWSR1-FLI1-dependent expression of a therapeutic payload as evidenced by episomal and CRISPR-edited genomic reporter assays. Combining in silico screens and immunohistochemistry, we identified GPR64 as a highly specific cell surface antigen for targeted transduction strategies in EwS. Functional experiments demonstrated that anti-GPR64-pseudotyped lentivirus harboring our expression cassette can specifically transduce EwS cells to promote the expression of viral thymidine kinase sensitizing EwS for treatment to otherwise relatively non-toxic (Val)ganciclovir and leading to strong anti-tumorigenic, but no adverse effects in vivo. Further, we prove that similar vector designs can be applied in PAX3-FOXO1-driven ARMS, and to express immunomodulatory cytokines, such as IL-15 and XCL1, in tumor entities typically considered to be immunologically 'cold'.Collectively, these results generated in pediatric sarcomas indicate that exploiting, rather than suppressing, the neomorphic functions of chimeric transcription factors may open inroads to innovative and personalized therapies, and that our highly versatile approach may be translatable to other cancers addicted to oncogenic transcription factors with unique DNA-binding properties.
Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease?
Authors: Silvia Rota, Daniele Urso, Daniel J. van Wamelen, Valentina Leta, Iro Boura, Per Odin, Alberto J. Espay, Peter Jenner, K. Ray Chaudhuri
Journal: Translational Neurodegeneration (2022)

Abstract Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson’s disease (PD) to control motor and non-motor fluctuations (‘OFF’ periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of ‘OFF’ periods. However, data suggest that despite their efficacy in reducing the number and duration of ‘OFF’ periods, these strategies still do not prevent ‘OFF’ periods in the middle to late stages of PD, thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation. Why these emergent ‘OFF’ periods still occur is unknown. In this review, we analyse the potential reasons for their persistence. The contribution of drug- and device-related involvement, and the problems related to site-specific drug delivery are analysed. We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent ‘OFF’ periods unresponsive to dopaminergic therapy delivered via CDD.
Hereditary cancer variants and homologous recombination deficiency in biliary tract cancer
Authors: Yuki Okawa, Yusuke Iwasaki, Todd A. Johnson, Nobutaka Ebata, Chihiro Inai, Mikiko Endo, Kazuhiro Maejima, Shota Sasagawa, Masashi Fujita, Koichi Matsuda, Yoshinori Murakami, Toru Nakamura, Satoshi Hirano, Yukihide Momozawa, Hidewaki Nakagawa
Journal: Journal of Hepatology (2022)
Tom Nolan’s research reviews—13 October 2022
Authors: Tom Nolan
Journal: BMJ (2022)

Little protection from cerebral embolic protectionI recently found myself sieving milk to remove any creamy bits that might render a bowl of Rice Krispies inadequate, and I realised I'd long since lost my authority as a parent.In cardiac surgery, they use the same principle (sieving out unwanted bits, rather than submissive parenting) in cerebral embolic protection (CEP) devices, designed to collect the debris that gets chucked into the carotid and vertebral arteries during transcatheter aortic valve replacement (TAVR).Use of CEP is supposed to reduce the risk of periprocedural stroke, an often devastating complication in around 4% of these procedures.A US based registry found that, since CEP devices were commercially approved, around 13% of TAVR procedures have used them.
Post-acute sequelae of covid-19 six to 12 months after infection: population based study
Authors: Raphael S Peter, Alexandra Nieters, Hans-Georg Kräusslich, Stefan O Brockmann, Siri Göpel, Gerhard Kindle, Uta Merle, Jürgen M Steinacker, Dietrich Rothenbacher, Winfried V Kern
Journal: BMJ (2022)

Abstract Objectives To describe symptoms and symptom clusters of post-covid syndrome six to 12 months after acute infection, describe risk factors, and examine the association of symptom clusters with general health and working capacity. Design Population based, cross sectional study Setting Adults aged 18-65 years with confirmed SARS-CoV-2 infection between October 2020 and March 2021 notified to health authorities in four geographically defined regions in southern Germany. Participants 50 457 patients were invited to participate in the study, of whom 12 053 (24%) responded and 11 710 (58.8% (n=6881) female; mean age 44.1 years; 3.6% (412/11 602) previously admitted with covid-19; mean follow-up time 8.5 months) could be included in the analyses. Main outcome measures Symptom frequencies (six to 12 months after versus before acute infection), symptom severity and clustering, risk factors, and associations with general health recovery and working capacity. Results The symptom clusters fatigue (37.2% (4213/11 312), 95% confidence interval 36.4% to 38.1%) and neurocognitive impairment (31.3% (3561/11 361), 30.5% to 32.2%) contributed most to reduced health recovery and working capacity, but chest symptoms, anxiety/depression, headache/dizziness, and pain syndromes were also prevalent and relevant for working capacity, with some differences according to sex and age. Considering new symptoms with at least moderate impairment of daily life and ≤80% recovered general health or working capacity, the overall estimate for post-covid syndrome was 28.5% (3289/11 536, 27.7% to 29.3%) among participants or at least 6.5% (3289/50 457) in the infected adult population (assuming that all non-responders had completely recovered). The true value is likely to be between these estimates. Conclusions Despite the limitation of a low response rate and possible selection and recall biases, this study suggests a considerable burden of self-reported post-acute symptom clusters and possible sequelae, notably fatigue and neurocognitive impairment, six to 12 months after acute SARS-CoV-2 infection, even among young and middle aged adults after mild infection, with a substantial impact on general health and working capacity. Trial registration German registry of clinical studies DRKS 00027012.
Emergence of BRCA Reversion Mutations in Patients with Metastatic Castration-resistant Prostate Cancer After Treatment with Rucaparib
Authors: Andrea Loehr, Arif Hussain, Akash Patnaik, Alan H. Bryce, Daniel Castellano, Albert Font, Jeremy Shapiro, Jingsong Zhang, Brieuc Sautois, Nicholas J. Vogelzang, Gurkamal Chatta, Kevin Courtney, Andrea Harzstark, Francesco Ricci, Darrin Despain, Simon Watkins, Charmin King, Minh Nguyen, Andrew D. Simmons, Simon Chowdhury, Wassim Abida
Journal: European Urology (2022)
Maternal colonization and early-onset neonatal bacterial sepsis in the Gambia, West Africa: a genomic analysis of vertical transmission
Authors: Uduak A. Okomo, Saffiatou Darboe, Saikou Y. Bah, Abigail Ayorinde, Sheikh Jarju, Abdul Karim Sesay, Ngange Kebbeh, Abdou Gai, Tida Dibbasey, Mary Grey-Johnson, Kirsty Le Doare, Kathryn E. Holt, Joy E. Lawn, Beate Kampmann
Journal: Clinical Microbiology and Infection (2022)

ObjectivesTo define bacterial aetiology of neonatal sepsis and estimate the prevalence of neonatal infection from maternal genital tract bacterial carriage among mother-newborn pairs.MethodsWe carried out a cross-sectional study of newborns with clinical sepsis admitted to three hospitals in the Gambia neonatal wards. Neonatal blood cultures and maternal genital swabs were obtained at recruitment. We used whole-genome sequencing to explore vertical transmission for neonates with microbiologically confirmed bloodstream infection by comparing phenotypically-matched paired neonatal blood cultures and maternal genital tract bacterial isolates.ResultsWe enrolled 203 maternal-newborn pairs. Two-thirds (67%; 137/203) of neonates presented with early-onset sepsis (days 0–6 after birth) of which 26% (36/137) were because of a clinically-significant bacterial pathogen. Blood culture isolates from newborns with early-onset sepsis because of Staphylococcus aureus (n = 5), Klebsiella pneumonia (n = 2), and Enterococcus faecalis (n = 1), phenotypically matched their maternal genital tract isolates. Pairwise single-nucleotide variants comparisons showed differences of 12 to 52 single-nucleotide variants only between maternal and newborn S. aureus isolates, presumably representing vertical transmission with a transmission rate of 14% (5/36).ConclusionsWe found a low prevalence of vertical transmission of maternal genital tract colonization in maternal-newborn pairs for early-onset neonatal sepsis in the West African context. Identifying infection acquisition pathways among newborns is essential to prioritize preventive interventions, which could be targeted at the mother or infection control in the hospital environment, depending on the major pathways of transmission.
Hope can bring solutions to climate despair
Authors: Kamran Abbasi
Journal: BMJ (2022)

Reaching the differential diagnosis of tuberculosis and sarcoidosis can be difficult due to granulomatous inflammation. Determining alkaline phosphatase (ALP) activity in serum for the differential diagnosis of tuberculosis and sarcoidosis. This study comprised 104 acid-fast bacilli (AFB) positive patients with pulmonary tuberculosis, 90 patients with biopsy-proven sarcoidosis and 43 healthy controls were included. ALP activity was measured at the first admission of the patients. There was a significant difference between the tuberculosis and the control (p= 0.03). Also, there was a significant difference between the tuberculosis and sarcoidosis (p= 0.034<i>)</i> According to the comparison of tuberculosis and sarcoidosis, the cut-off value was determined as 71.50 IU/L, which had sensitivity of 80%, specificity of 51%, PPV of 66%, NPV of 69%, accuracy of 67%, and the AUC was 0.728. ALP, as a little-known marker for tuberculosis and sarcoidosis, was increased in the pulmonary tuberculosis compared with the sarcoidosis. As such, it may be a useful tool for the differentiation of tuberculosis and sarcoidosis.